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Biomedical subjects

R G Cooks

Publications and source records attributed to R G Cooks.

At least 37 records · Page 2Linked to original sources
PubMed1994

Analysis of nucleotides and oligonucleotides immobilized as self-assembled monolayers by static secondary ion mass spectrometry.

Nucleic acid constituents can be bound to a metal surface in the form of self-assembled monolayers. Binding is achieved either through ionic interactions with a self-assembled 2-aminoethanethiol monolayer or by direct covalent binding of a dithiophosphate oligonucleotide to a metal surface through a sulfur-metal bond. Nucleotides, polynucleotides (both normal and a dithiophosphate analog) and double-stranded DNA have all been bound to surfaces. When the surfaces are interrogated using static secondary ion mass spectrometry (SIMS), the surface-bound nucleic acid constituents are observed in the form of the characteristic protonated nucleic acid base ions (BH2+). While a silver foil substrate was found to provide the highest absolute signal, vapor-deposited gold yields the best signal-to-noise ratio for ionically bound deoxyguanosine monophosphate. Under comparable conditions, a Cs+ projectile produces a 10-fold increase in the secondary ion signal relative to a Ga+ projectile. The experiment has been extended to a triple-quadrupole instrument where tandem mass spectrometric experiments on ionically immobilized dGMP showed the characteristic loss of ammonia from the released BH2+ ion. When a 'biomimetic' surface formed by ionically immobilizing double-stranded DNA is exposed to a solution containing ethidium bromide, ions corresponding to the non-covalent adduct are readily detectable using SIMS. This adduct and the nucleic acid constituents can be monitored at levels below 10 fmol.

DNA↗
PubMed1994

Determination of taxanes in Taxus brevifolia extracts by tandem mass spectrometry and high-performance liquid chromatography.

A tandem mass spectrometric (ms/ms) method using desorption chemical ionization is described for the quantitation of taxol [1], cephalomannine [2], and baccatin III [3] found in Taxus brevifolia bark and needle extracts. A parent ion scan was used to simultaneously determine the weight percentages of 1-3 in bark and needle samples by the method of standard addition. In an alternative experiment, the concentration of 1 in the same samples was determined by ms/ms using trideuterated 10-acetyltaxol [7a] as an internal standard. High-performance liquid chromatography (hplc) was also used to determine the weight percentages of 1-3 in the same T. brevifolia bark and needle extracts with an external standard. The ms/ms method of quantitation by internal standard is the best overall method of analysis examined. With this method, 1 was quantitated in the T. brevifolia extracts at the low picomole level with a relative standard deviation of 17% or better for all samples analyzed with an analysis time of less than five min per sample. The precision, level of quantitation, and speed of analysis of the three methods of taxane quantitation are compared.

Alkaloids↗
PubMed1993

A rapid screening method for artemisinin and its congeners using ms/ms: search for new analogues in Artemisia annua.

A rapid screening method based on tandem mass spectrometry (ms/ms) is described for artemisinin-related compounds present in complex matrices. These compounds produce abundant ammonium adducts, [M + NH4]+, using ammonia desorption chemical ionization (dci), and dissociation of the mass-selected adducts yields the protonated molecules, [M + H]+, which subsequently eliminate characteristic neutral molecules (H2O, CO, HCO2H, HOAc). Neutral loss ms/ms scans which are selective for different elimination reactions were used in order to screen for groups of related analogues present in a crude hexane extract of Artemisia annua. Comparison of ms/ms product spectra of known Artemisia compounds with those of the new analogues provided information on the functional groups and the molecular weights of the new compounds present in the plant, and tentative structures are suggested.

Antimalarials↗
PubMed1992

Rapid screening for taxanes by tandem mass spectrometry.

A highly specific and sensitive method is described for determining taxol, cephalomannine, and baccatin III in crude plant extracts. Radical anions of the taxanes are formed by desorption chemical ionization, and a parent tandem mass spectrometric scan is used to recognize these compounds by their characteristic dissociations. The limit of detection of the individual taxanes in typical plant matrices is less than 500 pg when all three species are screened simultaneously. Because of the sensitivity of the method, extraction times can be shortened to 30 min and crude extracts can be examined at the rate of 6/h. Detection of all three taxanes extracted from a single Taxus cuspidata needle in a combined extraction/analysis time of less than 1 h is demonstrated.

Alkaloids↗
PubMed1991

Thermospray liquid chromatography-mass spectrometry with a quadrupole ion trap mass spectrometer.

A theromospray ion source using corona discharge ionization was interfaced to a quadrupole ion trap mass spectrometer via a multi-element lens system. Ions were injected into the trap periodically where they were stabilized by collisions with helium bath gas. Mass spectra were recorded on the trapped ions using the mass-selective instability scan mode. Data are shown for a peptide and a nucleoside and the effects of some experimental variables on the spectra are explored.

Adenosine↗
PubMed1991

Chemical modification of DNA: quantitation of O6-methyldeoxyguanosine by tandem mass spectrometry.

Methodology is described which allows quantitation of O6-methyldeoxyguanosine generated as a product of in vitro methylation of calf thymus DNA by methyl methanesulfonate (MeMS). Quantitative precision of 10% is achieved on samples of 10(-11)-10(-12) mol generated in 0.02% yield (expressed as O6-methyldeoxyguanosine versus deoxyguanosine) when DNA is treated with the weak carcinogen MeMS. These results show the potential application of this method to the analysis of DNA chemical modifications at the low levels that are relevant to the induction of biological effects of many alkylating agents. The methodology utilizes enzymatic degradation, reverse-phase chromatography and finally analysis by tandem mass spectrometry using desorption chemical ionization. Multiple reaction monitoring was used to increase sensitivity and the CD3-labeled nucleoside was used as an internal standard for quantification.

Chromatography, High Pressure Liquid↗
PubMed1990

Mass spectrometry and its use in tandem with laser spectroscopy.

Mass spectrometry is undergoing rapid development, especially with the extension of its range into the hundreds of kilodaltons, the emergence of the quadrupole ion trap as a high-performance instrument, and the development of techniques for recording three-dimensional spectra. These advances are summarized in this review; in addition, the power of the combination of lasers and mass spectrometers is given particular emphasis. Their combination has contributed recently to chemical dynamics, to the study of cluster structure and reactivity, and to the elucidation of the properties of highly excited molecules and ions.

Blood Chemical Analysis↗
PubMed1990

Systematic delineation of scan modes in multidimensional mass spectrometry.

A logical analysis of mass spectrometric scan modes is performed that reveals the full set of experiments available in multidimensional mass spectrometry. The analysis utilizes a symbolism that helps provide an organizational scheme for the representation and classification of the wide variety of experiments that exist. In general, for an n-stage experiment, there is a closed set of experimental modes producing spectral types that vary in mass dimensionality from 0 to n. There is a total of 2n experiments that have 1 or 0 mass dimensions, along with an increasing number of experiments of higher mass dimensionality. There also exists a set of 2n fundamental scan modes, viz., experiments in which only mass-to-charge ratios of individual ions, but not their interrelationships, are specified. Scans in which functional relationships between ion masses are defined (e.g., neutral loss scans) introduce complexity into the total number of scan types available in an MSn experiment, giving a total of 1, 2, 5, 15, 52, and 203 experiments of 0 through 5th order, respectively. It is shown that combinations of data from lower order experiments can be used to construct higher order spectra. Extraction of data of lower mass dimensionality from data of higher dimensionality is also demonstrated. A different method of reducing dimensionality, projection of dispersed data back into a smaller number of mass dimensions, is also introduced and characterized. The analysis reveals several new types of scan modes including an MS/MS/MS scan having unit mass dimensionality, referred to as the selective neutral-loss scan, and several new MS/MS/MS scans that are two-dimensional in mass. Examples of these new experiments are provided, and their potential value is discussed.

Mass Spectrometry↗
PubMed1988

Nucleophilic reactions between biological conjugates and tetraalkylammonium ion pair reagents during desorption chemical ionization.

Tetraalkylammonium salts, commonly used as ion pair reagents in chromatography, were found to react with biological conjugates under desorption chemical ionization conditions in a mass spectrometer. The reactions occur for aromatic glucuronide and glucoside conjugates using solid samples loaded on the direct exposure probe. Evidence is presented that several mechanisms contribute to the degradative alkylation of benzo(a)pyrene glucuronide. This undesirable process can be prevented by using ammonium or trialkylammonium instead of tetraalkylammonium salts in the chromatographic separation. Nucleophilic attack on the tetraalkylammonium cations in the energized condensed phase was found to occur also for some simpler aromatic compounds.

Chemical Phenomena↗
PubMed1987

Characterization of an alkylated dinucleotide by desorption chemical ionization and tandem mass spectrometry.

A highly sensitive (subpicomole level), structure-specific method of analysis has been developed for characterizing and quantitating the dinucleotide thymidylyl(3'----5')thymidine methyl phosphotriester by desorption chemical ionization tandem mass spectrometry. The methodology can be applied to related compounds such as the parent dinucleotide and employs either positive or negative ionization mass spectra or daughter spectra. The procedure allows specification of the site of methyl attachment.

Chemical Phenomena↗
PubMed1986

Modification of calf thymus DNA by methyl methanesulfonate. Quantitative determination of 7-methyldeoxyguanosine by mass spectrometry.

Quantitation of 7-methyldeoxyguanosine (m7dG) produced in the in vitro methyl methanesulfonate (MeMS) action on calf-thymus DNA is achieved by enzymatic degradation, liquid chromatographic separation and chemical ionization mass spectrometry. The total degree of methylation, measured by uptake of [14C]MeMS was 0.35%. Mass spectral analysis shows that m7dG constitutes 84% of the total methylated product. It is also shown that tandem mass spectrometry allows detection of m7dG, as the protonated base, down to 1 pmol level, suggesting that MS/MS analysis can be the method of choice in quantitation of the adducts of in vivo DNA modifications.

Animals↗
PubMed1985

Chemical modification of nucleic acids. Methylation of calf thymus DNA investigated by mass spectrometry and liquid chromatography.

Mass spectrometry provides an extremely sensitive method for the identification and quantification of modified nucleosides and hence for determining chemical modifications of nucleic acids. When mass spectrometry is used in conjunction with a new high-performance liquid chromatographic system capable of separating 15 methylated and naturally occurring nucleosides, this allows the quantification of products of in vitro DNA methylation. With synthetic (2H3)methyl-labeled methylnucleosides as internal references, the distribution of methylated products formed when calf thymus DNA was reacted with N-methyl-N-nitrosourea(MeNU) was determined. Five modified products, 1-methyldeoxyadenosine(m1dA), 3-methyldeoxycytidine(m3dC), 7-methyldeoxyguanosine(m7dG), 3-methylthymidine(m3T) and O4-methylthymidine(m4T) were detected and the relative distributions were measured. The ability of mass spectrometry/mass spectrometry (tandem mass spectrometry) to increase specificity and sensitivity in this determination is demonstrated and its application to in vivo studies is suggested.

Animals↗
PubMed1985

A new nail dysplasia syndrome with onychonychia and absence and/or hypoplasia of distal phalanges.

A family in which two generations have a rare and previously undescribed form of nail dysplasia with bone abnormalities is reported. This disorder is characterized by onychodystrophy, anonychia, brachydactyly of the fifth digit of the hands, and digitalization of the thumbs, with absence and/or hypoplasia of the distal phalanges of the hands and feet. The probable mode of transmission is autosomal dominant.

Abnormalities, Multiple↗